Answers to common and uncommon questions that come up during the course of ICU rounds at the University of Virginia Medical Center. Curated and developed by Jordan Hackworth, M.D.

Friday, November 12, 2010

ICU Rounds Report - Nov 12th 2010

We're back! I've been in the TCV-PO, where there was neither time nor medical students to help with the report. Now, the 'break' is over. Thanks for reading!

Colchicine is commonly used for both acute treatment and the prevention of gouty arthiritis. We've recently had a patient inadvertently continued on their home dose, which is problematic for many reasons. But first some background, and an interesting aside about American drug policy. The FDA has made arrangements for companies to test drugs grandfathered into common usage prior to the approval process in exchange for a few years of market exclusivity. Ostensibly, this is because the FDA cannot afford to run the trials themselves. Colchicine, despite being used for centuries, was recently approved (2009) after a drug company paid for a large clinical trial that proved efficacy according to modern FDA standards. Accordingly, exclusive approval to market the drug was given to URL Pharma and they promptly raised the price per tablet from $0.08 to $4.85, a move expected to cost Medicare over $50,000,000 this year alone. So, where's the savings?But I digress. How does it work? The drug has several effects, including decreasing urate cyrstal deposition, its primary therapuetic effect. Unfortunately, it also has potent anti-mitotic effects, poisoning the mitotic spindle in a dose-related manner. It's side effects are related mostly to this and are seen in sites with rapidly dividing cells: anemia, neutropenia, GI mucosal sloughing leading to upset, gastritis, etc. More severe overdosing looks like arsenic poisoning and causes renal failure, pulmonary hemorrhage, shock and death. Needless to say, the drug should routinely be held in critically ill patients. For the rare ICU patient dealing with acute gout, corticosteroids remain a much better choice.Kesselheim AS, Solomon DH (June 2010). "Incentives for drug development--the curious case of colchicine". N. Engl. J. Med.362 (22): 2045–7.The Perfect PEEP? The ARDS net trial seems to have helped settle the question of what tidal volumes we should be using, but finding the best PEEP level has been a harder question to settle. Based on the ARDSnet recommendations, our current practice (basically whatever amount above 5 cm H2O that is needed to oxygenate) does not take into account individual characteristics such as chest wall and lung compliance that might have an impact. Three large trials comparing high to low PEEP (ALVEOLI, LOVS and EXPRESS studies) have been done and each showed some improvement in oxygenation with more PEEP, but have not shown a mortality benefit. Now, a group at Harvard has published the results of a small, single ICU pilot trial using intraesophageal ballons measuring (hopefully!) transpulmonary pressure, allowing PEEP to be adjusted based on individual respiratory compliance curves. The results of the pilot are positive and show improvement in recruitment, compliance and oxygenation. Whether this will result in a clinically meaningful benefit can only be shown with a much bigger trial, but the idea is exciting. Maybe Stuart could combine this with a NAVA catheter and we'll have found the perfect ventilator strategy?Talmor D, Sarge T, Malhotra A, O'Donnell CR, Ritz R, Lisbon A, Novack V, Loring SH: Mechanical ventilation guided by esophageal pressure in acute lung injury. N Engl J Med 2008, 359:2095-2104Beta Blockers for Respiratory Failure. A soon-to-be published paper in Critical Care Medicine reminds us once again that patients admitted on beta-blockers do much, much better when they are continued. This paper, using data from the BASEL II ICU trial, evaluates patients admitted to an ICU with respiratory failure, of any cause. In this mixed group of non-septic patients admitted with respiratory failure (pneumonia, heart failure, asthma, COPD and pulmonary embolism) those on beta-blockers at the time of admission had much lower 28 day and one year mortality (OR 0.32 [0.18 – 0.52] P<0.0001), regardless of the eitology of the respiratory failure. Further, discontinuing beta-blockers at admission was found to be quite hazardous in this group (one year mortality 82 vs 41%, P <0.000001). Patients who were not on beta-blockers at the time of admission but placed on them prior to discharge had their mortality rate reduced by a third (p<0.001).These results are a retrospective look at prospective data from a trial evaluating something else (B-type natriuretic peptide -guided management strategy on short-term outcome). Causality isn't proven with these results and they don't therefore justify placing patients admitted with respiratory failure on beta-blockers. They do, however, add a another shovel to the growing mountain of evidence that patients on beta-blockers at the time of admission should, whenever possible, have the beta-blockers continued. They also raise the question of whether beta-blockers should be used routinely for respiratory failure. Prior to this paper, that suggestion seemed crazy (metoprolol for asthma? carvedilol for acute PE?!)That question needs further study.Noveanu M, et al. Effect of oral beta-blocker on short and long-term mortality in patients with acute respiratory failure: results from the BASEL-II-ICU Study Critical Care 2010, [in press] 14:R198 doi:10.1186/cc9317Noveanu M, et al. Use of B-Type Natriuretic Peptide in the Management of Hypoxemic Respiratory Failure. Eur J Heart Fail 2010:[in press].